Structure of a Novel O-Linked N-Acetyl-d-glucosamine (O-GlcNAc) Transferase, GtfA, Reveals Insights into the Glycosylation of Pneumococcal Serine-rich Repeat Adhesins

Shi, Wei; Jiang, Yong-Liang; Zhu, Fan; Yang, Yi; Shao, Qiu Yan; Yang, Hong; Ren, Yi; Wu, Hui; Chen, Yuxing; Zhou, Cong‐Zhao

doi:10.1074/jbc.m114.581934

Cited by 48 publications

(54 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2A). As expected for a GT-B fold glycosyltransferase and observed in a structure of ligand-bound GtfA alone (25,34,35), UDP and GlcNAc reside in the cleft between the two R folds. Compared with the apo structure of GtfA, the R-fold II rotates toward R-fold I by ∼20°, thereby embracing the sugar and nucleotide and narrowing the cleft between the R folds (Fig.…”

Section: Resultssupporting

confidence: 76%

“…S1A). As reported (25), GtfA has a GT-B structure with two Rossmann-like folds (R folds I and II) and an extended β-sheet domain (EBD; also called DUF1975), which together give the molecule a horseshoe-like shape (Fig. 1B).…”

Section: Resultsmentioning

confidence: 72%

“…GtfA contains the residues in the active site that are typical for GT-B fold glycosyltransferases, including E404 that is needed for catalysis and K333 and R328 that are involved in binding the phosphates of the UDP-GlcNAc substrate (25,34,35) (Fig. 2C).…”

Section: Resultsmentioning

confidence: 99%

“…quality of the data. Molecular replacement was performed with PHASER in the PHENIX software suite (50), using a published S. pneumoniae GtfA structure (PDB ID code 4PQG), lacking the R-fold II, as the initial search model (25). Two copies of GtfA were identified in each asymmetric unit.…”

Section: Methodsmentioning

confidence: 99%

“…Structural studies on GtfA from Streptococcus pneumoniae show that it belongs to the GT-B family of glycosyltransferases and contains a binding site for UDP-GlcNAc (25). According to the CAZy classification, GtfA is a member of the GT4 family and retains the stereochemistry of the anomeric bond of the sugar during the enzymatic reaction (26,27).…”

Section: Significancementioning

confidence: 99%

See 4 more Smart Citations

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Chen

Seepersaud

Bensing

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

O-glycosylation of Ser and Thr residues is an important process in all organisms, which is only poorly understood. Such modification is required for the export and function of adhesin proteins that mediate the attachment of pathogenic Gram-positive bacteria to host cells. Here, we have analyzed the mechanism by which the cytosolic O-glycosyltransferase GtfA/B of Streptococcus gordonii modifies the Ser/Thr-rich repeats of adhesin. The enzyme is a tetramer containing two molecules each of GtfA and GtfB. The two subunits have the same fold, but only GtfA contains an active site, whereas GtfB provides the primary binding site for adhesin. During a first phase of glycosylation, the conformation of GtfB is restrained by GtfA to bind substrate with unmodified Ser/Thr residues. In a slow second phase, GtfB recognizes residues that are already modified with N-acetylglucosamine, likely by converting into a relaxed conformation in which one interface with GtfA is broken. These results explain how the glycosyltransferase modifies a progressively changing substrate molecule.

show abstract

Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

See 3 more Smart Citations

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Chen

Seepersaud

Bensing

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Pathogen-Host Infection Via Glycan Recognition and Interaction

Kim

2022

Glycobiology of Innate Immunology

View full text Add to dashboard Cite

Insights into bacterial protein glycosylation in human microbiota

Zhu

2015

Sci. China Life Sci.

Self Cite

View full text Add to dashboard Cite

The study of human microbiota is an emerging research topic. The past efforts have mainly centered on studying the composition and genomic landscape of bacterial species within the targeted communities. The interaction between bacteria and hosts is the pivotal event in the initiation and progression of infectious diseases. There is a great need to identify and characterize the molecules that mediate the bacteria-host interaction. Bacterial surface exposed proteins play an important role in the bacteria-host interaction. Numerous surface proteins are glycosylated, and the glycosylation is crucial for their function in mediating the bacterial interaction with hosts. Here we present an overview of surface glycoproteins from bacteria that inhabit three major mucosal environments across human body: oral, gut and skin. We describe the important enzymes involved in the process of protein glycosylation, and discuss how the process impacts the bacteria-host interaction. Emerging molecular details underlying glycosylation of bacterial surface proteins may lead to new opportunities for designing anti-infective small molecules, and developing novel vaccines in order to treat or prevent bacterial infection.

show abstract

Structure of a Novel O-Linked N-Acetyl-d-glucosamine (O-GlcNAc) Transferase, GtfA, Reveals Insights into the Glycosylation of Pneumococcal Serine-rich Repeat Adhesins

Cited by 48 publications

References 62 publications

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Mechanism of a cytosolic O -glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Pathogen-Host Infection Via Glycan Recognition and Interaction

Insights into bacterial protein glycosylation in human microbiota

Contact Info

Product

Resources

About